1. The role of Notch and TGF-β pathways in CD4+ T cell responses
- Author
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Corsin-Jimenez, Marta
- Subjects
616.079 - Abstract
Notch receptors (1 to 4) are highly conserved cell surface molecules that bind two different families of ligands, Delta (1, 3 and 4) and Serrate (1 and 2, Jagged in vertebrates). Notch signalling plays a fundamental role in cell fate decisions during embryogenesis in both invertebrates and vertebrates, the best-characterised example of this is neurogenesis in Drosophila. This process involves the specification of neural versus epidermal precursors. The aim of this study was to investigate further the potential role of components of the Notch pathway and TGF-β superfamily members in CD4
+ cell responses in vitro and in vivo. The first question addressed if these developmentally related molecules were expressed in lymphoid organs and cells of adult mice. I used reverse transcriptase polymerase chain reaction (RT-PCR) to demonstrate that these molecules are expressed in adult lymphoid compartments, and real-time PCR revealed that activating CD4+ T cells and B cells in vitro differentially regulated genes of the Notch signalling pathway and of the TGF-β superfamily. Secondly I investigated if components of the Notch signalling pathway were modulated in murine splenic CD4+ T cells in response to peptide delivered intranasally under conditions that induce tolerance or priming. Furthermore, I phenotyped the CD4+ T cells in an attempt to characterise the regulatory T cells generated during tolerance induction. Finally, I carried out in vitro experiences to investigate the functional effects of the TGF-β-like molecules, activin A and BMP-4, on murine splenic CD4+ T cells and how these effects correlated with expression of components of the Notch signalling pathway.- Published
- 2002